Abstract

In the midbrain ventral tegmental area (VTA), both dopaminergic and nondopaminergic neural substrates mediate various behavioural reward phenomena. VTA GABAergic neurons are anatomically positioned to influence the activity of both the mesolimbic dopamine system and nondopamine efferents from the VTA. In order to examine the possible functional role of VTA GABAA receptors in neural reward processes, we performed discrete, bilateral microinjections of the GABAA receptor agonist, muscimol, or the GABAA receptor antagonist, bicuculline, into the VTA. Using a fully counterbalanced, unbiased conditioned place-preference paradigm, we demonstrate that activation of VTA GABAA receptors, with the GABAA receptor agonist muscimol (5–50 ng/µL), or inhibition of VTA GABAA receptors, with the GABAA receptor antagonist bicuculline (5–50 ng/µL), both produce robust rewarding effects. Furthermore, these rewarding effects can be pharmacologically dissociated: blockade of dopamine receptors with a dopamine receptor antagonist, α-flupenthixol (0.8 mg/kg; i.p.), or concurrent activation of VTA GABAB receptors with a GABAB receptor agonist, baclofen (70 ng/µL), blocked the rewarding properties of the GABAA receptor agonist, but had no effect on the rewarding properties of the GABAA receptor antagonist. These results suggest that, within the VTA, a single GABAA receptor substrate controls bidirectional reward signalling between dopaminergic and nondopaminergic brain reward systems.